Ocular toxicity of intravitreous adalimumab (Humira) in the rabbit

Manzano, Roberta Munhoz; Peyman, Gholam A.; Carvounis, Petros; Kivilcim, Muhamet; Khan, Palwasha; Chévez-Barrios, Patricia; Takahashi, Walter Yukihiko

doi:10.1007/s00417-008-0765-z

Cited by 39 publications

(34 citation statements)

References 23 publications

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“…In the current study we did not find any toxic effect, even though we used a fivefold greater dose (5 mgr/0.1 ml) than the 1.0 mg/ 0.1 ml used by Manzano et al [28] which demonstrated toxic effects. Differences in the composition of the administered drug may explain the differences observed in high-dose toxicity.…”

Section: Discussioncontrasting

confidence: 64%

“…A recent study in the literature by Manzano et al [28], investigating intravitreal toxicity of adalimumad in rabbit eyes, concluded that doses 0.2 and 0.5 mg/0.1 ml do not demonstrate any toxic effects; however, administration of 1.0 mg/0.1 ml was associated with an inflammatory reaction in two animals and retinal necrosis in one animal out of the three tested [28]. In the current study we did not find any toxic effect, even though we used a fivefold greater dose (5 mgr/0.1 ml) than the 1.0 mg/ 0.1 ml used by Manzano et al [28] which demonstrated toxic effects.…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Evaluation of potential retinal toxicity of adalimumab (Humira)

Tsilimbaris

Diakonis

Naoumidi

et al. 2009

Graefes Arch Clin Exp Ophthalmol

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Section: Discussioncontrasting

confidence: 64%

Section: Discussionmentioning

confidence: 98%

Evaluation of potential retinal toxicity of adalimumab (Humira)

Tsilimbaris

Diakonis

Naoumidi

et al. 2009

Graefes Arch Clin Exp Ophthalmol

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“…One study recently demonstrated the safety profile of intravitreal injections of various doses of adalimumab in rabbits. Their results showed normal retinal examination in eyes having received injections of balanced salt solution (BSS), 0.25 or 0.50 mg adalimumab; however, 1 mg adalimumab induced inflammatory changes, retinal histopathological alterations and significant ERG reduction [102] . In summary, most studies suggest a dose-dependent retinal toxicity profile for intravitreal anti-TNF mAbs, and further evaluation should determine the exact safe dosage for each drug.…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Retinal and Ocular Toxicity in Ocular Application of Drugs and Chemicals – Part II: Retinal Toxicity of Current and New Drugs

et al. 2010

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Aims: Retinal pharmacotherapy has gained great importance for the treatment of various retinal diseases. An increasing number of drugs have been constantly released into the market, especially for wet age-related macular disease and diabetic macular edema. In this review, the issues concerning the toxicity of current and new classes of drugs are discussed. Methods: An extensive search of the literature was performed to review various aspects of drug toxicity in retinal pharmacotherapy. The different major classes of drugs, such as corticosteroids, antibiotics, antimetabolites, antineoplastic agents, monoclonal antibodies (mAbs), nonsteroidal anti-inflammatory drugs, enzymes, fibrinolytics, miscellaneous anti-inflammatory and antiangiogenic agents, as well as toxicity unrelated to the drug were identified and discussed. Results: Corticosteroids like fluocinolone, dexamethasone or triamcinolone at low dose cause little damage to the retina, but at high doses signs of toxicity have been well documented. Complications like cataract and glaucoma are quite common with corticosteroids. Aminoglycosides showed differences in the type and doses associated with toxic reactions, thereby the following order of toxicity can be described (from most toxic to least toxic): gentamicin > netilmicin = tobramycin > amikacin = kanamycin. Vancomycin at the usual dose of 1 mg is not toxic to the retina, while further studies are necessary in order to clarify the safety of new-generation quinolones. 5-Fluorouracil has been shown to be nontoxic to the retina after an injection of 2.5 mg in animals. mAbs like ranibizumab and bevacizumab were demonstrated to be safe to the retina in cell culture, animals and humans at high doses. The exact biocompatibility of nonsteroidal anti-inflammatory agents like diclofenac needs further evaluation. Preservatives like benzyl alcohol and changes in pH or osmolarity exert an influence on the toxic effects of intravitreally applied drugs. Conclusions: A great number of drugs are now used mainly intravitreally without relevant retinal toxicity.

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“…Moreover, intravitreal injections of infliximab may lead to serious intraocular inflammation. 21 On the other hand, IVA did not lead to retinal damage in animal models at a dose of 0.5 mg in one study 22 and up to 5 mg in another study. 23 No information is available on the stability and efficacy of reconstituted or aliquoted adalimumab for multiple use to date.…”

Section: Discussionmentioning

confidence: 92%